PMP201 Infection ISU: Antibiotics Part 3

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Questions and Answers

What structure in Mycobacteria contributes to its resistance against antibiotics?

Protein rich cell wall

Thick, hydrophobic, and waxy cell wall (correct)

Thin peptidoglycan layer

Presence of beta-lactamase enzymes

Which of the following drugs is NOT part of the initial treatment regimen for newly diagnosed tuberculosis?

Streptomycin (correct)

Isoniazid

Ethambutol

Rifampicin

What type of tuberculosis is resistant to both Rifampicin and Isoniazid?

Latent TB

MDR-TB (correct)

XDR-TB

Drug sensitive TB

Which staining method is primarily used for the microbiological diagnosis of Mycobacteria?

Acid-fast staining Signup and view all the answers

Which component is inhibited by Isoniazid in the treatment of tuberculosis?

Mycolic acid synthesis Signup and view all the answers

Which antibiotic class targets transpeptidase enzymes through a β-lactam ring structure?

β-lactams Signup and view all the answers

What mechanism do glycopeptide antibiotics primarily use to display their antibacterial activity?

Disrupting cell wall synthesis Signup and view all the answers

Inhibitors that act on nucleic acid synthesis primarily interfere with which of the following processes?

DNA replication and transcription Signup and view all the answers

Which of the following classes is NOT associated with inhibiting protein synthesis?

Glycopeptides Signup and view all the answers

What is a primary mechanism of action for Nitrofurantoin?

Generating reactive free radicals Signup and view all the answers

Which antibacterial mechanism involves inhibiting the formation of peptide cross-links in peptidoglycan strands?

Inhibition of cell wall synthesis Signup and view all the answers

Which of the following side effects is specifically associated with Metronidazole?

Metallic taste and furred tongue Signup and view all the answers

Which of these components is primarily targeted by the proteins involved in the inhibition of protein synthesis?

Ribosomes Signup and view all the answers

In which scenario should Nitrofurantoin be avoided?

In patients with G6PD deficiency Signup and view all the answers

Which mechanism is characteristic of antimetabolite antibiotics?

Mimicking substrates involved in metabolic pathways Signup and view all the answers

What is the recommended action when a patient is prescribed Metronidazole?

Avoid alcohol consumption Signup and view all the answers

Which of the following statements about tuberculosis is accurate?

It can have both latent and active forms. Signup and view all the answers

What type of organism is Mycobacterium tuberculosis classified as?

Gram-positive and aerobe Signup and view all the answers

What serious side effect is associated with Nitrofurantoin?

Pulmonary toxicity Signup and view all the answers

Which category of patients should be particularly cautious when using Nitrofurantoin?

Patients with decreased renal function Signup and view all the answers

Which of the following symptoms may indicate a rare but serious side effect of Metronidazole?

Peripheral neuropathy Signup and view all the answers

What major worldwide impact did tuberculosis have in 2021?

It affected over 10 million individuals. Signup and view all the answers

What is a key mechanism by which metronidazole exerts its bactericidal effect?

Generation of free radicals Signup and view all the answers

Which adverse effect is associated with the use of rifampicin?

Rapid development of resistance Signup and view all the answers

Which patient group is contraindicated for the use of rifampicin?

Patients with acute porphyrias Signup and view all the answers

What is the primary action of clindamycin in bacterial cells?

Block the translocation process Signup and view all the answers

What type of bacteria does metronidazole specifically target?

Anaerobic bacteria Signup and view all the answers

Which statement about oxazolidinones is true?

They specifically target the large subunit of the ribosome. Signup and view all the answers

Which of the following is NOT a side effect of rifampicin?

Renal failure Signup and view all the answers

What is the mechanism of action of sulphonamides?

Competition with PABA to inhibit DHPS Signup and view all the answers

What is necessary for metronidazole to be activated in bacterial cells?

Low redox potential Signup and view all the answers

Which class of antibiotics has a suffix indicating its mechanism involving faulty protein synthesis?

-mycin Signup and view all the answers

What effect do nitroimidazoles have on bacterial DNA?

DNA fragmentation Signup and view all the answers

What is the primary action of cytochrome P450 in relation to rifampicin?

Induction of drug metabolism Signup and view all the answers

How does trimethoprim exhibit selective toxicity?

Because it has higher affinity for bacterial DHFR Signup and view all the answers

Which of the following statements accurately describes chloramphenicol's mechanism of action?

It blocks tRNA from entering the ribosomal site A Signup and view all the answers

Which condition is treated with metronidazole?

H.pylori eradication Signup and view all the answers

In what way does rifampicin affect body fluids?

Causes harmless discoloration Signup and view all the answers

What role do antimetabolites play in antibiotic therapy?

They selectively inhibit key bacterial enzymes Signup and view all the answers

What is the primary consequence of using aminoglycosides in bacterial treatment?

Faulty or premature proteins due to mRNA misreading Signup and view all the answers

Which antibiotic specifically targets dihydrofolate reductase in bacterial cells?

Trimethoprim Signup and view all the answers

Study Notes

PMP201 - Infection ISU: Antibiotics - Drug Classes and Mechanisms - Part 3

Course: PMP201 Infection ISU
Topic: Antibiotics - Drug Classes and Mechanisms - Part 3
Date: 6th November 2024
Lecturer: Dr. Giulio Nannetti

Previous & Complementary Knowledge

Health, Disease & Patient (PMP101) 2023/24: Microbiology lectures - Bacteria composition, Bacterial growth.
Patient-Centred Learning I (PMP201) 2024/25: Overview of antibiotics (1, 2 & 3) from Dr. Guirguis. Chemistry of antibiotics from Dr. Padalino.

Learning Outcomes

Antimetabolite Antibiotics: Outline the antibacterial mechanism, effect, and properties of the main types.
Nucleic Acid Synthesis Inhibitors: Outline the antibacterial mechanism, effect, and properties of inhibitors of nucleic acid synthesis.
Alternative Mechanism Antibiotics: Outline the antibacterial mechanism, effect, and properties of antibiotics acting with an alternative mechanism of action.
Therapeutic Agents for Tuberculosis: Identify the therapeutic agents for tuberculosis.

Mechanism of Actions - Recap

Inhibition of Cell Wall Synthesis: ẞ-lactams (penicillins, cephalosporins, monobactams, carbapenems), Glycopeptides (vancomycin).
Inhibition of Nucleic Acid Synthesis: Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), Rifamycins (rifampin).
Inhibition of Protein Synthesis: Aminoglycosides, Tetracyclines, Macrolides, Lincosamines, Chloramphenicol, Oxazolidinones.
Acting as Antimetabolites: Primarily targeting key enzymes to block folic acid synthesis (essential for nucleotide production) - Sulphonamides, Trimethoprim.

3) Antibiotic classes acting as antimetabolites

Inhibit bacterial metabolic pathways (distinct from those in eukaryotic cells)
Selective toxicity - Primarily target key enzymes to block folic acid synthesis; essential for nucleotide production.
Bacteriostatic effect.

3a) Sulphonamides

Sulfamethoxazole mechanism: Folic acid is essential to produce purines (nucleotides). Bacteria cannot uptake folic acid from outside. Bacteria synthesize folic acid, starting from a precursor p-aminobenzoic acid (PABA). Sulphonamides act by competing with PABA to inhibit the first enzyme dihydropteroate synthase (DHPS). In human body - Folic acid (Vitamin B9) obtained in the diet.

3b) Trimethoprim

Trimethoprim mechanism: Trimethoprim targets dihydrofolate reductase (DHFR). DHFR is present in human cells, for the dietary folic acid activation. Selective toxicity: Trimethoprim has 100,000x higher affinity for bacterial DHFR over human counterpart.

3a+b) Sulphonamides + trimethoprim (co-trimoxazole)

Sequential blocking mechanism: Both drugs block the folic acid synthesis at two distinct steps → potential synergistic effect.
Bacteriostatic effect.
Spectrum: Broad (Gram+ve and Gram-ve).

3a+b) Sulphonamides + trimethoprim (co-trimoxazole) - Side effects/Contraindications/Cautions

Side effects: Risk of folate deficiency (during pregnancy, associated with neural tube defects), Hyperkalaemia, Hypersensitivity (rash and anaphylaxis)
Contraindications: Avoid in first-trimester of pregnancy, patients with blood dyscrasias, in acute porphyria, elderly, neonates, and predisposition to folate deficiency.

4) Inhibition of nucleic acids synthesis

DNA synthesis: Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin).
RNA synthesis: Rifamycins (rifampicin)

4a) Fluoroquinolones

Mechanism: Inhibit DNA replication by interfering with bacterial topoisomerases (2 types). DNA gyrase (not present in humans) is targeted. Topoisomerase IV (human enzyme) is inhibited at high doses.
Spectrum: Broad (effective against Gram +ve and -ve).
Uses: Serious RTIs (CAP), skin/soft tissue infections, and UTIs (E. coli). Systemic fluoroquinolones must be prescribed when other options are inappropriate.
Side Effects: GI distress, tendonitis, tendon rupture, muscle weakness, joint pain, prolonged QT interval, aortic aneurysm (rare), seizures (rare), peripheral neuropathy).
Contraindications/Cautions: Patients with history of tendon damage, taking corticosteroids, QT prolongation risk factors, in epilepsy, psychiatric disorders, or patients with renal impairment, exposure to sunlight.

4b) Rifamycins (Rifampicin)

Mechanism: Inhibits the initiation of bacterial DNA transcription by blocking bacterial RNA polymerase activity.
Bactericidal effect.
Spectrum: Broad (Gram +ve and -ve), and Mycobacteria.
Uses: Tuberculosis, N. meningitidis/H. influenzae meningitis (enters cerebrospinal fluid).
Side Effects: GI distress, minor hepatotoxicity, discoloration of body fluids (urine and sweat turn orange - harmless), many interactions (inducing cytochrome P450).
Contraindications: Patients with acute porphyrias.

5) Alternative mechanisms

Nitroimidazoles (Metronidazole): Generates unstable metabolites leading to DNA fragmentation, Bactericidal effect.
Nitrofurantoin: Generates reactive free radicals, interfering with RNA, DNA and other components synthesis. Bactericidal effect.

5a) Nitroimidazoles (Metronidazole)

Mechanism: Generating free radicals in bacteria. Reduced form generates an unstable nitroso radical metabolite (ROS). ROS leads to DNA fragmentation.
Spectrum: Only anaerobes (including protozoa). Activated/reduced by low redox potential within cells.
Uses: Treat infections of anaerobic bacteria, H. pylori eradication
Side Effects: Gastrointestinal distress, metallic taste, furred tongue, peripheral neuropathy (rare), disulfiram-like adverse reactions with alcohol.
Cautions: Avoid exposure to sunlight with topical use, avoid intravaginal preparations in young girls, and avoid alcohol.

5b) Nitrofurantoin

Mechanism: Generating reactive free radicals; interfering with RNA, DNA and other components synthesis.
Spectrum: Effective against most Gram +ve and some Gram -ve (E. coli).
Uses: Treat and prevent uncomplicated acute UTIs.
Side effects: Discoloration of body fluids (urine and sweat), pulmonary toxicity (fever, chills, cough), peripheral neuropathy (rare), blood disorders (rare).
Contraindications: Decreased renal function (eGFR < 45 mL/min), G6PD deficiency, infants (less than 3 months old). In anaemia, diabetes, electrolyte imbalances, and folate deficiency.

Treatment for Tuberculosis (TB)

10.6 million people fell ill with TB in 2021, 1.6 million died.
Types of TB: Pulmonary (infection in the lungs) or Extrapulmonary (spread to other organs). Latent (asymptomatic) and Active (symptomatic).
Mycobacterium tuberculosis: Gram+ve, aerobe, complex and unique cell wall. Important virulence factors, markers (acid-fast/auramine fluorescent staining (mycolic acids)).
Cell Wall of Mycobacteria: Thick, hydrophobic, robust and waxy (variety of lipids); hydrophobic barrier to antibiotics.
Treatment for TB: First-line drugs (RIPE): Rifampicin (RNA polymerase inhibitor), Isoniazid (inhibitor of mycolic acids synthesis), Pyrazinamide (interferes with fatty acid synthesis), and Ethambutol (interferes with arabinogalactans synthesis).
Newly diagnosed/re-treatment therapies: Different protocols based on the stage (initial phase and continuation).
Drug-resistant strains: Multidrug-resistant TB (MDR-TB) and Extensively drug-resistant TB (XDR-TB).

Quiz Questions

Trimethoprim target: Folic acid synthesis.
Not a first-line TB drug: Amoxicillin.

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Description

This quiz covers the mechanisms and effects of various classes of antibiotics, focusing on antimetabolite antibiotics, nucleic acid synthesis inhibitors, and alternative mechanism antibiotics. Designed for students of the PMP201 Infection ISU course, it reinforces key concepts essential for understanding antibiotic actions in clinical settings.